Autism is a severe developmental disorder characterized by impairment in social interactions and communication and by stereotyped movements with no agreed upon etiology or treatment. The goal of this project is to assess the role of proopiomelanocortin (POMC) peptides in autistic children. Children were chosen since there may be a developmental aspect ot this phenomenon. Since a majority of autistics are also mentally retarded (MR), it will be determined if there is a different relationship between opioid and nonopioid POMC peptides in MR versus NMR autistic subjects. Some of the symptoms of autism including the failure to seek social attachments and the occurrence of self-injurious behavior may reflect over-activity in some brain opioid system as well as a dysfunction of the POMC system of the hypothalamic-pituitary-adrenal (HPA) axis. The specific aims of this projects are to: (1) assess the treatment efficacy and safety of the opioid receptor antagonist, naltrexone, in autism, (2) evaluate the usefulness of naltrexone as a pharmacological tool for defining the status of the POMC HPA axis in autism, (3) determine if there are differences in plasma POMC peptides in autistics versus controls, and (4) determine if the effects outlined in 1, 2 and 3 vary as a function of MR versus NMR status. All subjects will be evaluated for autism by two psychiatrists, and for MR by a clinical psychiatrist. Autistic subjects will be divided into the MR and NMR groups using developmentally appropriate psychometric tests. First, behavioral, biochemical, cardiovascular and physical effects of naltrexone will be evaluated in twenty autistic children (N=10 MR, N=10 NMR, 3 to 13 years of age) using a conservative FDA approved four phase protocol. Behavioral measures for assessing naltrexone effects include the BRC Autism and Self-Injury Scales, CARS, ABC, CPTRS, BRC Social Proximity test, BOS, PPVT-R and the Vineland Adaptive Behavior Scale. Cardiovascular and physical measures include heart rate, blood pressure, EKG, body temperature, body weight and serum concentrations of the liver enzymes SGOT and SGPT. Biochemical measures include plasma concentrations of naltrexone and select POMC related peptides such as B-endorphin, ACTH, and cortisol. Phase I (acute study) is an ascending dose-response in which placebo or naltrexone (0.5, 1.0, 1.5 and 2.0 mg/kg) is administered once per week. Phase II (chronic study) is an ascending dose-response in which placebo or naltrexone (0.5, 1.0, 1.5 and 2.0 mg/kg) is administered every other day three times a week. Phase III is an attenuated double-blind design where placebo, 1.0 and 2.0 mg/kg naltrexone are each administered every other day for one week with sequence determined by a Latin square. Phase IV is a double-blind cross-over design where placebo and naltrexone (1.0 mg/kg) are each administered daily for four weeks. All sessions will be videotaped for blind behavioral analyses.